促炎性细胞因子IL6通过gp130-JAK1/STAT1/3-HIF1α/ERRα轴抑制线粒体功能
Jianing Xu1, Matthew Wakai1, Kun Xiong2
1Aging/Age-Related Diseases, Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, USA.
Cell reports
|March 8, 2025
概括
慢性炎症,标志着interleukin-6 (IL6),通过抑制PGC1表达来损害线粒体功能. 抑制IL6通路可能会恢复老化中的线粒体健康.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 免疫学 免疫学 免疫学
背景情况:
- 慢性炎症和线粒体功能下降是衰老的关键指标.
- 炎症和线粒体衰退之间的相互作用尚未完全理解.
研究的目的:
- 为了研究介质素-6 (IL6) 与老化中的线粒体功能障碍之间的联系.
- 阐明调解IL6诱导的线粒体功能抑制的分子机制.
主要方法:
- 研究了JAK1/STAT1/3信号轴的作用.
- 分析了HIF1α和ERRα转录和蛋白质稳定性的调节.
- 评估了PGC1表达对IL6治疗下线粒体呼吸的影响.
主要成果:
- 当PGC1的表达率较低时,IN-6 (IL6) 抑制了线粒体的功能.
- JAK1/STAT1/3轴激活HIF1α,这反过来又抑制ERRα,这是线粒体生物发生的关键调节者.
- 升高的PGC1水平拯救ERRα,即使暴露于IL6,也增强了线粒体呼吸.
结论:
- IL6诱导的炎症可以通过JAK1/STAT1/3/HIF1α/ERRα通路损害线粒体功能.
- PGC1在维护线粒体功能以抵抗炎症攻击方面发挥着至关重要的作用.
- 针对IL6信号轴为与年龄相关的线粒体功能障碍的潜在治疗策略.
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